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Cardiac defects are the most common type of birth defect. An infant with a cardiac defect is more likely to die from this type defect than other types of defects (Forrester 2002). An atrial septal defect (ASD) is a defect or hole in the septum between the two atria of the heart. ASDs are typically divided into several categories depending on the part of the atrial septum where the defect occurs:
- Secundum ASD (also called ASD 2 or ASD II) - defect is in the midportion of the atrial septum concerning the fossa ovalis.
- Primum ASD (also called ASD 1 or ASD I) - defect is in the endocardial cushion section of the atrial septum and is typically grouped with other endocardial cushion defects such as endocardial cushion ventricular septal defect and atrioventricular canal.
- Sinus venous ASD - defect is in the upper portion of the atrial septum near the entry of the superior vena cava.
In one investigation, ASDs of known type consisted of 77% secundum, 20% primum, and 2% sinus venous (Ferencz 1997). Occasionally the available medical records will not mention the location of the ASD. Sometimes a secundum ASD cannot be distinguished from a large patent foramen ovale (PFO) and the diagnosis of "PFO versus secundum ASD" is reported. PFO is not considered an ASD for most analyses. ASD accounts for 3%-22% of reported congenital heart defects (Becker 2001, Botto 2001a, Borgmann 1999, Samanek 1999, Jaiyesimi 1993, Kidd 1993, Pradat 1992, Fixler 1990, Tikkanen 1991a, Tikkanen 1990, Stoll 1989, Grabitz 1988, Ferencz 1985).
ASSOCIATED BIRTH DEFECTS
While atrial septal defect can occur independently, approximately 25%-40% of ASD cases have other cardiac and non-cardiac birth defects (Ferencz 1997, Stoll 1993, Pradat 1992, Castilla 1990). Chromosomal abnormalities have been reported for 6%-14% of secundum ASD cases (Ferencz 1997, Stoll 1989). ASD occurs with trisomy 21, accounting for 7%-26% of the congenital heart defects observed among trisomy 21 cases (Boldt 2002, Freeman 1998, Kallen 1996). ASD is also found with trisomy 18, trisomy 13, Holt-Oram syndrome, VACTERL association, and fetal alcohol syndrome (Goldmuntz 2001, Tennstedt 1999, Torfs 1998, Ferencz 1997). ASD is connected with the 22q11 deletion that is linked to DiGeorge syndrome, velo-cardio-facial syndrome, and several other syndromes (Borgmann 1999). One investigation reported 20% of cases with ASD that did not have other chromosomal abnormalities had 22q11 deletion (Trost 1999). Other studies observed ASD among 1%-2% of patients with 22q11 (Marino 2001, Ryan 1997).
ASD can be detected prenatally through ultrasound or fetal echocardiography, although the accuracy of diagnosis may not be high and may depend on the type of specialist performing the examination (Boldt 2002, Berghella 2001, Meyer-Wittkopf 2001). Part of the problem with diagnosing ASD prenatally is the difficulty in distinguishing between PFO and ASD. Prenatal diagnosis rates have been reported to be between 0%-8% (Stoll 2002, Garne 2001, Stoll 1998, Montana 1996, Papp 1995, Stoll 1993). One investigation reported the prenatal diagnosis rate of ASD to increase over time (Stoll 2002).
Although ASD may be prenatally diagnosed, the elective termination rate for the defect is low, with studies reported rates of 0%-0.8% (Boldt 2002, Wren 2000, Papp 1995, Stoll 1993). Most ASD cases result in live birth, with only 8 -10% being identified among fetal deaths (Forrester 2002, Botto 2001a, Garne 2001). The first-year survival rate for ASD is 93%-94% (Samanek 1999, Ferencz 1997). One investigation reported a decline in the infant mortality rate due to atrial and ventricular septal defects combined during 1985-1997 (Lee 2001).
DEMOGRAPHIC AND REPRODUCTIVE FACTORS
Studies of risk of ASD by race/ethnicity have been inconsistent (Table 2). While several studies observed no difference in ASD risk between whites and African-Americans (Correa-Villansenor 1991, Chavez 1988), other studies found higher ASD rates among African-Americans or nonwhites (Botto 2001a, Ferencz 1997, Fixler 1993). One study found significantly lower rates of atrial septal defects among whites than any other group (Forrester 2002). One investigation reported ASD rates to be lowest among Hispanics and highest among Native Americans (Chavez 1988).
Secular and Seasonal Trends
ASD rates have increased over the last several decades (Botto 2001a, Ferencz 1997), although this may be due to the increased use of echocardiography (Forrester 2002). The increased use of echocardiography results in the discovery of small defects that may not have been diagnosed previously. Reports of the seasonal variation of ASD risk have been mixed. Several studies reported seasonal variation of secundum ASD rates (Ferencz 1997, Bound 1989) while other investigations reported no significant seasonal variation for ASD (Tikkanen 1991b, Tikkanen 1990, Samanek 1991a).
Secundum ASD has been reported to be more frequent in urban areas (Ferencz 1997). A study in Czechoslovakia reported regional differences in rates of ASD (Samanek 1991b).
Secundum ASD is less common among males (Lary 2001, Ferencz 1997, Sampayo 1994), or ASD shows no association with infant sex (Samanek 1994, Rothman 1976).
One investigation described risk of secundum ASD to be increased with three or more previous pregnancies (Ferencz 1997) while another investigation reported increased risk of ASD among firstborn infants (Rothman 1976).
Various studies have noted increased risk of ASD among twins (Mastroiacovo 1999, Ferencz 1997, Layde 1980).
Gestational Age and Birth Weight
Secundum ASD risk increases with lower gestational age (Ferencz 1997). ASD is also associated with low birth weight (Ferencz 1997), macrosomia (Waller 2001), and small for gestational age (intrauterine growth retardation) (Ferencz 1997, Rosenthal 1991, Khoury 1988).
One investigation reported increased risk of ASD among the offspring born to first cousins (Becker 2001).
Several studies reported no association between ASD risk and maternal age (Baird 1991, Tikkanen 1992a, Tikkanen 1990) while another investigation observed increased secundum ASD risk with maternal age of 30 years or more (Ferencz 1997). Another study concluded that there was a significant increased risk of atrial septal defect with advanced maternal age, even when cases with chromosomal abnormalities were excluded (Forrester 2002). Secundum ASD is not associated with paternal age (Ferencz 1997, Tikkanen 1992a).
Socioeconomic Status (SES)
One investigation noted increased risk of secundum ASD with lower maternal education but no association between the secundum ASD and annual household income or paternal education (Ferencz 1997). A second study indicated that there was a higher risk for all non-chromosomal defects among individuals with low socioeconomic status (Vrijheid 2000).
FACTORS IN LIFESTYLE OR ENVIRONMENT
Maternal Illnesses and Conditions
One study that examined the relationship between maternal pre-pregnancy weight and ASD risk noted higher ASD risk with maternal overweight condition, although the association was not statistically significant (Watkins 2001). More recent studies have indicated that there is a significant risk for congenital anomalies, including atrial septal defects, in the offspring of women who are clinically obese (Watkins 2003). A second, similar study indicated that obese non-diabetic African-American women were more significantly more likely to have babies with cardiac defects (Mikhail 2002).
Several studies have reported an association between ASD and maternal diabetes (Loffredo 2001a, Ferencz 1997) while a third study did not (Becerra 1990). ASD has been reported among the offspring of mothers with phenylketonuria (Levy 2001).
There is no association between ASD and influenza (Ferencz 1997), hypothyroidism (Khoury 1989), or hyperthyroidism (Khoury 1989). Increased risk of secundum ASD has been observed with maternal urinary tract infection (Ferencz 1997).
Investigations of the relationship between ASD risk and maternal hyperthermia have produced mixed results. One investigation observed no association of ASD with febrile illness or flu-associated fever (Botto 2001b) while a second study reported no association of ASD with workplace temperature, sauna bathing, or upper respiratory infection but increased risk of ASD with fever (Tikkanen 1991b).
One study reported increased risk of secundum ASD with maternal corticosteroid use (Ferencz 1997). ASD does not appear to be associated with maternal use of ampicillin (Czeizel 2001), misoprostol (Orioli 2000), or acetylsalicylic acid (Tikkanen 1992a, Tikkanen 1991b). Other drugs known to cause cardiac defects including atrial septal defect include: busulfan, lithium, reinoids, thalidomide, and trimetadione, as well as insulin, antihypertensives, erythromycin, naproxen, anticonvulsants, nitrifurantoin, clomipramine, and budesonide in nasal preparations (Mone 2004).
Maternal multivitamin use does not affect ASD risk (Botto 2000). However, an investigation reported increased risk of ASD with maternal fever and no multivitamin use; however, risk was reduced with multivitamin use (Botto 2002)
Maternal coffee consumption did not influence ASD risk (Tikkanen 1992a, Tikkanen 1991a), nor does maternal consumption of tea, cocoa, and cola (Tikkanen 1992a).
While several studies reported no association between maternal alcohol use and ASD risk (Ferencz 1997, Tikkanen 1990), another investigation observed increased risk of ASD with maternal alcohol use (Tikkanen 1992a). Atrial septal defects are sometimes associated with Fetal Alcohol Syndrome (FAS) (Mone 2004).
One study reported increased risk of ASD with maternal smoking (Kallen 1999) while other investigations found no such association (Ferencz 1997, Tikkanen 1992a, Tikkanen 1991a).
ASD does not appear related to maternal exposure to pesticides (Loffredo 2001b), dyes, lacquers, paints, wood preservatives, plastic raw materials, glues, microwave ovens, video display terminals, anesthetic gases, textile dusts at work (Tikkanen 1991a) or organic solvents at work (Tikkanen 1992b). However, a more recent study indicated that exposure to organic solvents does increase the likelihood of a cardiac defect (Mone 2004).
A study that examined the relationship between proximity of various industries to place of residence found no association between the industries and ASD (Castilla 2000). ASD is not associated with ionizing radiation occupational exposure (Ferencz 1997), carbon monoxide or ozone air pollution exposure (Ritz 2002), or chlorination and natural organic matter in the water supply (Hwang 2002). A recent review article reported increased risk of ASD with paternal occupation of forestry and logging worker, fire fighter, painter, carpenter and wood worker, and jewelry making (Chia 2002). Another study reported ASD to be associated with paternal exposure to paint stripping, solvents, extreme cold temperature, and laboratory work with viruses (Ferencz 1997). Secundum ASD risk may be elevated with paternal cocaine use or smoking more than 20 cigarettes per day (Ferencz 1997).
The birth prevalence in the United States for atrial septal defect ranges between 13.63 and 100.18 per 10,000 live births (National Birth Defects Prevention Network 2005). The rate in Texas for 1999-2002 deliveries was 40.12 cases per 10,000 live births. Differences in prevalence may be due to differences in case inclusion criteria and/or regional differences in diagnostic practices.
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Please Note: The primary purpose of this report is to provide background necessary for conducting cluster investigations. It summarizes literature about risk factors associated with this defect. The strengths and limitations of each reference were not critically examined prior to inclusion in this report. Consumers and professionals using this information are advised to consult the references given for more in-depth information. This report is for information purposes only and is not intended to diagnose, cure, mitigate, treat, or prevent disease or other conditions and is not intended to provide a determination or assessment of the state of health. Individuals affected by this condition should consult their physician and when appropriate, seek genetic counseling.